Retinopathy is a non-inflammatory degenerative disease of the retina that leads to visual field loss or blindness. Retinopathy can be caused by various ophthalmic conditions as well as numerous systemic diseases outside the eye, for example diabetes. Diabetic retinopathy is an eye disease that results from damage to the retina as a result of complications such as nerve damage arising from diabetes mellitus. Diabetic retinopathy affects more than 80% of all patients who have had diabetes for 10 years or more and is the leading cause of vision loss in developed countries (Aiello et al., 1998).
Many retinal disorders can be diagnosed with the aid of retinal examination. Fluorescein angiography (FA) is the current standard technique used in diagnosis of diabetic retinopathy (DR) and is useful in detecting late-stage clinical hallmarks of DR, including retinal neovascularization (Saine, 1993). Laser photocoagulation, which has been applied in DR treatment for over half a century (Antonetti et al., 2006), is also a late-stage based treatment. Laser photocoagulation is successful in arresting proliferative diabetic retinopathy (PDR) in only 50% of cases. Even where further degeneration is prevented, any vision loss already incurred cannot be restored (Schwartz and Flynn, 2007).
Neuronal cell death in the retina (i.e. neuropathy) has been implicated in the early stages of DR, occurring much earlier than vascular damage becomes evident via FA techniques (Antonetti et al., 2006; Leith et al., 2000; Lorenzi et al, 2001; Gardner et al., 2002; Smith, 2007; Serrarbassa et al., 2008). Diabetic neuropathy affects the entire spectrum of retinal neurons, including the ganglion, horizontal, amacrine and photoreceptor cells (Antonetti et al., 2006; Smith, 2007). In fact, a reduction in the thickness of the neuronal cell layers in the retina due to diabetes has been reported in both experimental mice and human patients (Leith et al., 2000).
Pupillary light reflex (PLR) refers to the dilation/constriction of the pupil in response to light reaching the retina. High intensity light on the retina results in constriction in order to reduce the total light reaching the retina, and conversely, low intensity light results in pupil dilation in order to increase the light entering the eye and reaching the pupil. PLR can provide a useful diagnostic tool, allowing for testing of the sensory and motor responses of the eye. Lesions or disruptions in the eye can be detected by testing the direct response of a particular eye exposed to light entering the pupil as well as the consensual response of the eye when the opposite eye is exposed to light entering the pupil.
PLR has conventionally been used in the clinical setting to characterize the early effects of diabetic neuropathy (Hreidarsson, 1982; Devos et al., 1989; Kuroda et al., 1989). Such methods involve direct measurement of the pupil diameter or area in response to intense light. A pupillometer light source is generally focused on the pupil area, since the emphasis is on obtaining a bright and contrasting pupil image so that the pupil area can be accurately measured. This is an important consideration particularly in cases where poor pupil-iris contrast is obtained.
However, the early effects of retinopathy, which include diabetic neuropathy, on PLR can only be objectively assessed if light is directed onto the site of possible disease, that is, the photoreceptive retinal neurons. Thus, in order to use PLR as an indicator of early retinopathy, not only must the intensity level of the light source be controlled, but also the amount of light that reaches the retina must also be controlled (Fountas et al., 2006), which can be complicated, since slight changes in lens opacity and matrix of the eye may affect the amount of light actually reaching the retina. The initial pupil size may also affect the amount of light incident on the retina and influence the resultant pupillary constriction. As well, monitoring PLR by direct measurement of pupil size, such as pupil area or diameter, does not take into account the amount of stimulus light incident on the retina. Determining and standardizing the amount of light incident on the retina during diagnosis can present difficulties, particularly in longitudinal and quantitative studies of retinopathy.
Effective early detection and preventive treatment of retinopathy, including diabetic retinopathy would help to minimize complications such as permanent vision loss due to late-stage treatment provided by laser photocoagulation.